학술논문
Association of Combined TCF7L2 and KCNQ1 Gene Polymorphisms with Diabetic Micro- and Macrovascular Complications in Type 2 Diabetes Mellitus.
Document Type
Academic Journal
Author
Rattanatham R; Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen, Thailand.; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.; Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat, Thailand.; Settasatian N; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.; School of Medical Technology, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen, Thailand.; Komanasin N; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.; School of Medical Technology, Faculty of Associated Medical Science, Khon Kaen University, Khon Kaen, Thailand.; Kukongviriyapan U; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.; Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.; Sawanyawisuth K; Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.; Intharaphet P; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.; Queen Sirikit Heart Center of the Northeast, Khon Kaen University, Khon Kaen, Thailand.; Senthong V; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.; Department of Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.; Queen Sirikit Heart Center of the Northeast, Khon Kaen University, Khon Kaen, Thailand.; Settasatian C; Cardiovascular Research Group, Khon Kaen University, Khon Kaen, Thailand.; Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Source
Publisher: Korean Diabetes Association Country of Publication: Korea (South) NLM ID: 101556588 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2233-6087 (Electronic) Linking ISSN: 22336079 NLM ISO Abbreviation: Diabetes Metab J Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Vascular complications are the major morbid consequences of type 2 diabetes mellitus (T2DM). The transcription factor 7-like 2 (TCF7L2), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and inwardly-rectifying potassium channel, subfamily J, member 11 gene (KCNJ11) are common T2DM susceptibility genes in various populations. However, the associations between polymorphisms in these genes and diabetic complications are controversial. This study aimed to investigate the effects of combined gene-polymorphisms within TCF7L2, KCNQ1, and KCNJ11 on vascular complications in Thai subjects with T2DM.
Methods: We conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications.
Results: The gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2-3 and GRS 5-6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]).
Conclusion: This study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.
Methods: We conducted a case-control study comprising 960 T2DM patients and 740 non-diabetes controls. Single nucleotide polymorphisms in TCF7L2, KCNQ1, and KCNJ11 were genotyped and evaluated for their association with diabetic vascular complications.
Results: The gene variants TCF7L2 rs290487-T, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-C were associated with increased risk of T2DM. TCF7L2 rs7903146-C, TCF7L2 rs290487-C, KCNQ1 rs2237892-T, and KCNQ1 rs2237897-T revealed an association with hypertension. The specific combination of risk-alleles that have effects on T2DM and hypertension, TCF7L2 rs7903146-C, KCNQ1 rs2237892-C, and KCNQ1 rs2237897-T, as genetic risk score (GRS), pronounced significant association with coronary artery disease (CAD), cumulative nephropathy and CAD, and cumulative microvascular and macrovascular complications (respective odds ratios [ORs] with 95% confidence interval [95% CI], comparing between GRS 2-3 and GRS 5-6, were 7.31 [2.03 to 26.35], 3.92 [1.75 to 8.76], and 2.33 [1.13 to 4.79]).
Conclusion: This study demonstrated, for the first time, the effect conferred by specific combined genetic variants in TCF7L2 and KCNQ1 on diabetic vascular complications, predominantly with nephropathy and CAD. Such a specific pattern of gene variant combination may implicate in the progression of T2DM and life-threatening vascular complications.